What are the Periodic Paralysis?
First, a simplified blurb on normal physiology:
Nerves are like electric wires that transmit signals from the brain to the muscles. Muscle cells have potassium and sodium on the inside and outside of their cell membranes. Muscle cells respond to nerve signals by letting ions change location from the inside to the outside and from the outside to the inside of their cell membranes. The ions cross the muscle membrane through ION CHANNELS. Each ion (i.e. sodium, potassium, calcium, and chloride) has its own channel.
Periodic paralysis and the non-dystrophic myotonias are diseases where people get muscle weakness and/or muscle stiffness. This happens because the ION CHANNELS in the muscle membrane are faulty. The faulty ion channels prevent the potassium and sodium from being where they need to be. The misplaced ions cause the ion channels to shut off inappropriately, causing weakness, or not to shut off inappropriately, causing stiffness.
Of the periodic paralyses and non-dystrophic myotonias, there are several different disease types that have been identified. A brief description of each disease follows. Please be aware that there are many people with overlapping symptoms (for example, they experience paralysis AND myotonia), there are a wide variety of symptoms that are not listed below, and that many people do not fit the exact mold of the classifications below (for example, acetazolamide does not help all patients with hypokalemic periodic paralysis and indeed can make some patients worse)
What is in general known about the different sub types?
What is Periodic Paralysis?
There are 6 subtypes
Hypokalemic Periodic Paralysis:
Genes: Sodium channel, Potassium Channel, Calcium channel
Secondary: Thyroid over-activity
Endocrine or renal problems: Certain substances and medications
Main Symptoms: weakness, low serum potassium; permanent muscle weakness
Main Triggers: carbohydrates, salt, rest after exercise, stress, cold, insulin
Things that Alleviate Attacks Acutely: potassium
Things that Prevent Attacks Chronically: acetazolamide, dichlorphenamide, spironolactone, triamterene, amiloride, proper diet, avoidance of triggers
Hyperkalemic Periodic Paralysis:
Genes: Sodium channel
Secondary: Renal problems
Main Symptoms: weakness, usually less duration than in hypokalemic periodic paralysis, myotonia (muscle stiffness that can be alleviated by exercise), high serum potassium; permanent muscle weakness
Main Triggers: potassium intake, rest after exercise, stress, hunger, cold
Things that Alleviate Attacks Acutely: Carbohydrates (simple sugars), insulin, albuterol, calcium injection
Things that Prevent Attacks Chronically: acetazolamide, dichlorphenamide, other potassium-wasting diuretics (e.g. hydrochlorothiazide), proper diet, avoidance of triggers
Andersen-Tawil Syndrome (ATS):
Gene: potassium channel
Definition: Periodic Paralysis (hyper or hypo), long QT syndrome, and skeletal abnormalities (wide spaced eyes, low-set ears, webbed fingers or toes)
Main Symptoms: weakness, palpitations, atypical attacks with muscle twitching (myoclonus); low or high serum potassium (depends on associated periodic paralysis)
Main Triggers: same as that for the type of periodic paralysis they have Things that Alleviate Attacks: same as that for the type of periodic paralysis they have
Things that Prevent Attacks Chronically: same as that for the type of periodic paralysis they have
Gene: Chloride channel
Main Symptoms: muscle stiffness
Main Triggers: sudden exercise, sudden noise
Things that Alleviate Attacks Acutely: repeated movement of stiff muscle (warm-up phenomenon)
Things that Prevent Attacks Chronically: mexilitene, acetazolamide, phenytoin, quinine, carbamazepine
Gene: sodium channel
Definition: muscle stiffness that worsens with exercise (paradoxical myotonia) and with cold
Main Symptoms: muscle stiffness followed by weakness, especially with exercise in cold weather; can be associated with hyperkalemic periodic paralysis; normal serum potassium; no warm-up phenomenon
Main Triggers: same as those for hyperkalemic periodic paralysis; cooling and heavy muscular work
Things that Alleviate Attacks Acutely: warm environment relieves stiffness, no therapy to relieve weakness acutely; same as for hyperkalemic periodic paralysis (if hyperkalemic periodic paralysis is a feature)
Things that Prevent Attacks Chronically: acetazolamide, mexilitene; same as for hyperkalemic periodic paralysis if that is a feature
Gene: Sodium channel
Main Symptoms: intermittent, generalized muscle stiffness; no weakness; not worsened by cold
Main Triggers: potassium ingestion; rest after exercise; succinylcholine anesthesia
Things that Alleviate Attacks Acutely: same as for hyperkalemic periodic paralysis
Things that Prevent Attacks Chronically: mexiletine, acetazolamide
No one in my family has this disease. How did I get it?
Periodic paralysis is a spectrum of neuromuscular disorders all resulting in episodes of weakness and/or paralysis occurring with variable frequency and lasting anywhere from a few minutes to days. There are two major recognized types of periodic paralysis: that with attacks of weakness caused by high blood levels of potassium, termed HYPERkalemic periodic paralysis, and that with attacks of weakness caused by low blood levels of potassium, termed HYPOkalemic periodic paralysis.
Hypokalemic periodic paralysis can have a number of causes:
- hyperthyroidism, a condition where your thyroid gland makes too much thyroid hormone, can cause hypokalemic periodic paralysis in susceptible patients;
- conditions where your body excretes (gets rid of) too much potassium for a number of reasons;
- a mutation in a gene coding for a calcium channel in your cells arises, causing you to have bouts of weakness. The third condition is called familial hypokalemic periodic paralysis and can be passed down from parent to child.
Say you have a family whose members have hypokalemic periodic paralysis. Say the child has it, the mom has it, and mom’s dad has it, and so on. Somebody in the family, way back when, had to be the first one to get the disease. He or she was unfortunate to get a mutation in the gene that causes this illness. Once one person has gotten the mutated gene, he or she can pass on the gene to future generations. So, if you are the first in your family to get the disease, this is possible. One must be aware that some people can carry the mutated gene, but for one reason or another, do not show signs of illness. So, you may not indeed be the first person in your family with the mutated gene. Then again, maybe you are.
Will I pass this on to my children and how does inheritance work?
Many cases of hypokalemic periodic paralysis have been proven to be caused by a mutation in a certain gene called the “DHP-sensitive calcium channel.” Healthy humans have one set of 23 genes from their mother and a corresponding set of 23 genes from their father. So, for the calcium channel gene, any human has two copies, one from mom and one from dad. When someone has a child, they pass on one of the two copies of a gene to their child, and their partner passes on the other copy to their child.
Now, let the good copy of the gene be labeled “g.” Let the bad copy be labelled “G.” Most humans have “g from mom” and “g from dad”. A hypokalemic periodic paralysis patient generally has “G from one parent” and “g from the other parent.” Now, let’s make a grid (called a Punnet square in the world of genetics): Say Mom has hypokalemic periodic paralysis.
What kinds of things trigger attacks? How can I determine what triggers my attacks?
Hypokalemic periodic paralysis patients describe a few triggers that apply to everyone: rest after exercise, high carbohydrate meals (that is, pasta, pizza, cakes, candy, sugar, rice, potatoes, french fries, etc.), and salty foods (that is, table salt, a.k.a. sodium chloride, a.k.a. NaCl).
Other triggers vary from person to person: alcoholic beverages, large meals, Chinese food (perhaps due to MSG), stress, cold weather, high humidity, dehydration, excessive bedrest, accidentally skipping doses of medications, viral illnesses such as the flu, diarrhea, and lack of sleep (this list is not comprehensive).
One method of discovering what triggers your own attacks is to keep a diary. This has proven useful to a number of people with periodic paralysis. You should first establish a grading system for your attacks: for example, mild = 1; moderate = 3; severe = 7; complete = 9.
Is it possible that a family with juvenile myoclonic epilepsy and Hypo PP for there to be a connection between these 2 diseases?
In general, it is unlikely for there to be a connection between these two diseases. The genetics behind juvenile myoclonic epilepsy is not worked out; however, given that we do not see the two disorders in a large number of patients, it would lead one to believe that they are unrelated. On the other hand, if indeed one has both, it would warrant research into the possibility of a relationship given that they are both so rare. Sorry to hedge on both sides of the fence!!!
Is there anything that helps for chronic cognitive impairment concerns?
I apologize but would need clarification of this question. I presume you mean “brain fog” associated with attacks of periodic paralysis, and possible continual “brain fog” from an attack that just won’t go away. In this case, proper treatment of the attack with appropriate medication would be the best strategy for alleviating the problem. Also, very strict avoidance of triggers, especially dietary triggers, would probably also help
Does PP cause Peripheral Neuropathy
PP has been associated with nerve conduction defects, but it is not commonly associated with peripheral neuropathy (at least sensory). The lack of muscles more likely could be from permanent muscle weakness due to intrinsic muscle damage from repeated attacks rather than from atrophy due to an injured nerve.
Can you better define Paramyotonia
Paramyotonia can occur along with hyperPP or by itself. It is characterized by worsening of the muscle stiffness with exercise, in contrast to myotonia congenita, which exhibits the warm-up phenomenon. Hence the name paramyotonia (short for paradoxical myotonia).
While our sailboat is in motion I have never had an attack in 6000 nautical miles. Ed sails sometimes day and night for 3-6 days. I have weakness attacks every few days when we are at anchor. Does this mean a mechanical rocking bed may prevent attacks?
This is an interesting observation, and is an interesting hypothesis. Without proper testing, I could not comment. That said, if it works for you, roll with it!
Is it a normal symptom to run out of breath and be tired after sweeping he kitchen floor?
No, this is not normal. Fatigue can have many causes, from cardiac to endocrine to neuromuscular to poor sleep hygiene to psychiatric. Your doctor should be able to sort it out. It is entirely possible that this is due to periodic paralysis, and one would expect the symptoms to be less with better control of the disease.
Will any of these medications trigger an attack? Zetia, Cymbalta, Diclofemac, Amlodepine?
Any medication can trigger an attack in anyone. That is, it is a case by case, trial and error type of discovery for each individual. That said, physiologically speaking, I would not expect any of these medications to be a significant trigger for periodic paralysis.
Can a person be Hypo Pp if their potassium while well (baseline) checked for a full month is in the range of 4.0-4.5?
Yes. The dip in potassium is seen only during attacks and is normal the other times.
Can a person be Hypo PP if attacks occur with potassium at 4.2 in some attacks and 4.6 in other attacks?
This would be atypical. However, if someone’s normal baseline is say, 4.8 and they get weak at 4.2 and get strong again after ingesting potassium, then one could make a good argument that the person may be hypoPP.
Can anything be done to create more awareness among doctors especially Neurologists in Ireland and other countries with this condition does exist and can be real especially if a patient presents as normal at consultation?
Awareness is a difficult thing to achieve for a rare disease. It is best to make the individual doctor aware of the disease. I wonder if we couldn’t make a program whereby the PPA sends literature or a physician awareness campaign to a specific physician that a member knows s/he is going to see. If literature comes from the PPA rather than from the patient, it may be better received. That said, the physician may become suspicious or skeptical at the coincidence of receiving literature and then seeing a patient the next week.
How do you convince Neurologists there is a benefit to do the CMAP EMG while a patient is on treatment?
The issue is what do you hope to gain from that test? It is typically a diagnostic test rather than a gauge of treatment success. I am sure that if you create a rational case, any reasonable physician would listen.
I have Hyper PP - what is the difference between HYPO and HYPER? Are the drugs used the same for both?
HyperPP gets worse when given potassium. A better term would be “potassium-sensitive PP”. HypoPP gets better when given potassium. A handful of drugs, specifically the carbonic anhydrase inhibitors – acetazolamide and dichlorphenamide – happen to work for both diseases for unclear reasons. Of course, this causes much confusion with patients and physicians, who prefer conceptualizing diseases and treatments as either “black or white”. (Maybe there is some good sense as to why the PPA logo is gray after all!!!)
Dr. L-H can you explain how the information you provided on HYPO would apply to HYPER?
In both instances, permanent muscle weakness is characterized by increased sodium content in muscle. By using diuretics to deplete the sodium from the muscle, we hypothesize that muscle strength will improve. In this way, the diuretic strategy would be expected to work for both hypoPP and hyperPP.
If Hypo and Hyper present opposite concerns re: potassium why do both respond to Diamox and Daranide?
This is somewhat of a mystery. There are a variety of theories. One good one is that these diuretics force you to excrete potassium, so this is good for hyperPP. In hypoPP, there are side currents in the calcium and sodium channels that are responsible for the faulty membrane potentials. These drugs appear to block these side currents in hypoPP. All in all, a strange coincidence!
Dr. L-H you say that if your K is normal between episodes this is a symptom of something other than PP
What I believe I said was that if the potassium is abnormal between episodes, it is likely not periodic paralysis but rather a renal or endocrine problem. That potassium is normal between episodes is a hallmark of periodic paralysis, and it is what makes it so difficult to diagnose.
Can permanent weakness be reversed?
Yes, with appropriate treatment, it can be reversed partially. It really depends on how advanced the permanent weakness is.
Do you recommend muscle biopsy and Na MRI as a diagnostic tool for patients? If so where is the NaMRI available? Is this a standard MRI?
As of now, the Na MRI is an investigational tool that has not made it into mainstream practice. We presented it at PPA to show you â€œcutting edgeâ€ research. One can demonstrate similar phenomena with a regular MRI. Muscle biopsy and MRI can help in the diagnosis or assessment of the extent of fixed weakness, but typically they are tertiary studies that are often not necessary in the diagnosis of periodic paralysis.
Is the Na MRI available in the USA?
Currently (2015), I am unaware of any center that offers this for clinical use in patients.
My wife was recently diagnosed with PP. Calcium Channel blockers have stabilized her condition. Why? And does this help explain if she is Hypo or Hyper?
This is an interesting observation that has been reported infrequently in the literature, most often with hypoPP patients. That said, one cannot rely on this information to render a diagnosis. We don’t know why that would work.
What effects do light weight lifting and other exercise have on my long-term prognosis for progressive weakness?
Weight lifting, in theory, tears muscle. As such, it should be avoided in theory. But, not controlled trial has looked at the value or detriment of weight-lifting in periodic paralysis to know for sure if it indeed does any damage at all. There is no reason to believe that patients with periodic paralysis have an impaired muscle repair capability. In general, patients should remain as active as possible. How much exercise they can do depends on what their individual threshold for inducing an attack of periodic paralysis is. If a particular exercise is inducing an attack then they are doing too much. For all patients with muscle disease, it is less desirable to do progressive resistive exercises meant to â€œbulk upâ€. Rather, patients should do more toning/aerobic types of exercises with less weight/resistance and more repetition. Specifically, eccentric contraction should be avoided.
Would a voltage converter help turn a nerve from a P2 to P1 level?
The ion channels do not work that way, but it is a nice thought. Ion channels reverse their states depending on the voltage across the muscle membranes. So, if we could arrange a â€œmicroâ€ voltage converter for each cell, it would be great. But, I believe it would be science fiction today.
Can a channelopathy cause low CO2 levels? Why?
I would not expect a channelopathy to cause low CO2 levels. If it did, I would not understand the mechanism. Acetazolamide and dichlorphenamide cause excretion of bicarbonate, resulting in a metabolic acidosis. The body will blow off more CO2 than usual to accommodate for that change. But this situation applies to treated patients.
Can a channelopathy affect ACTH levels? Why?
Probably not. Certainly we have not found that periodic paralysis affects ACTH levels.
At what point do I call 911? Respiratory difficulty, throwing up, can't swallow?
This is a personal question with no routine good answers. Anytime you feel your life is in danger, you should call 911. Respiratory difficulty and trouble swallowing are reasonable reasons for calling 911.
Why does PP affect only skeletal muscles except when it affects heart and respirations? What other exceptions are there?
The mutant ion channels are primarily found in skeletal muscle in the case of periodic paralysis. Respirations are controlled by skeletal muscle. I am not sure I understand what you mean by exceptions. We suspect the GI tract can slow down during a paralysis attack. For Andersen-Tawil Syndrome, the mutant potassium channels can also be found in the heart muscle. Electrical disturbances of the heart can occur due to low or high potassium in the blood without having a mutated ion channel located in the heart muscle itself.
What causes the pain with PP?
One possibility is the swelling of the muscle during a weakness spell that compresses pain-mediating nerve endings in the muscle.
What is the correlation between PP and myoclonic and Dystonic Activity?
Patients with hyperkalemic periodic paralysis can demonstrate paramyotonia. This is not universal.
Why does a person react to Diamox?
Positively or negatively? And in which disease? For some people with hypokalemic periodic paralysis, acetazolamide cause ill-feeings, usually within a day or two of taking the drug. We don’t know why this occurs. In terms of benefit, for hyperkalemic periodic paralysis, causing potassium-diuresis is felt to be the main mechanism of action. In hypokalemic periodic paralysis, correction of alkalosis is felt to play a role. In both disorders, we suspect there is also some direct effect on the abnormal ion channel currents as well.
Why does a person also have success with Spironolactone?
Spironolactone is a potassium-sparing diuretic, so it prevents the kidney from excreting potassium. In doing so, blood potassium levels are kept more elevated than they otherwise would be, and this is thought to prevent attacks of weakness. Spironolactone also excretes sodium, which is felt to collect pathologically in affected muscles.
What connection if any is there between PP and arthritis and also juvenile RA?
We do not believe there is a connection.
What are ways to increase muscle strength and muscle stamina once it is lost? PT brings on muscle weakness and paralysis. Is there any help for permanent muscle weakness?
Optimizing therapy is one way of doing so. This entails trial and error with different kinds, doses, and combinations of diruetics, diet, and in the case of hypokalemic periodic paralysis, potassium supplements.
Is sleep paralysis connected to this disorder?
Sleep paralysis is an unrelated disorder, but it often is on the differential diagnosis of periodic paralysis.
What meds affect Hypo negatively?
Potassium-wasting diuretics cause low potassium and thereby trigger attacks. Medications with glucose in them can also be problematic as glucose causes endogenous insulin secretion, which drives potassium into cells causing hypokalemia and thereby inducing an attack. Epinephrine and related adrenergic agonists (like albuterol) can also drive potassium into cells. Asthmatic and insulin-dependent diabetic patients with periodic paralysis are among the most difficult to manage. Periodic paralysis patients can be triggered by any medication unpredictably on a case-by-case basis.
How important is blood pressure variations and blood pressure control to the long-term progression of this disease?
I am unaware of any correlation between blood pressure control and periodic paralysis. That said, certain blood pressure medications are diuretics (either potassium wasting or potassium sparing) and/or potassium-sparing (i.e., ACE inhibitors). While these medications serve to control blood pressure, they can positively or negatively affect a person’s periodic paralysis depending on which type of disease a person has.
Why is alcohol such a trigger for many of us?
Alcohol is felt to cause electrolyte disturbances and dehydration, especially during recovery from the alcohol in the hours after indulging. Because alcohol is a depressant of inhibitions in small to moderate doses, we may do things we are not aware of during drinking ” like dietary indiscretion or physical activity beyond our normal comfort level. This may play a role.
Do we have any understanding of how Hypo PP can have initial onset at age 54? Is it possible to have symptoms and a mutation after surgery?
It is not likely that surgery can cause an ion channel mutation that would mutate all the body’s ion channels in all the muscles cells of the body. This would have to occur in the egg, sperm, or shortly after fertilization. We do not understand why periodic paralysis can become evident in some individuals near birth and in others late in life.
What do you consider an aggressive dose of a potassium sparing diuretic such as Amiloride? I take 10mg of Amiloride and 750mg of Diamox. Could I take more Amiloride?
This is a consideration that must be made with your doctor. In general, Amiloride, when given by itself, is labeled for doses between 5-20mg.
Is exon skipping (per MDA magazine) at all applicable to PP?
In short, probably not. The ion channels involved in periodic paralysis are felt to be necessary for life, such that fully mutated proteins are likely not compatible with life. The mutations we see in periodic paralysis are of one base pair in DNA resulting in one change in the amino acid sequence of the affected ion channel.
Is it common for patients with PP to have a mixed presentation of PP, mitochondrial disease and hemiplegic migraine?
This would certainly not be common, and, statistically speaking, it borders on impossible.
Is it possible to take large doses of K (100-120 daily) if you do not have PP or a kidney K wasting disease?
It is possible to do so. I would be concerned about elevating serum potassium and causing arrhythmias.
I have PP episodes at 4.0-3.8
This is always a tricky subject. If the diagnosis is indeed periodic paralysis, then one should think about the disease as: 1) potassium administration makes weakness better (hypokalemic periodic paralysis), or 2) potassium administration makes weakness worse (hyperkalemic periodic paralysis, and a better term might be potassium-sensitive paralysis). That said, hyperkalemic periodic paralysis patients sometimes require potassium. The term normokalemic is confusing and antequated. It has referred to patients that have either hyperkalemic or hypokalemic periodic paralysis whose attacks of weakness correspond with serum potassium measurements in the normal range. Indeed, we suspect that in such cases, there is either a relative hyperkalemia or hypokalemia in the individual, whereby the abnormal value is either lower or higher than the non-weak baseline but still within the normal reference range for potassium. It is difficult to recommend a particular target potassium level in such cases. It is not unreasonable to shoot for a level of 4.5 in a hypokalemic periodic paralysis patient that gets attacks of weakness at 4.0.
Has a precedent been set for pre-diagnosis of Andersen Tawil in IVF and is embryo selection possible?
Preterm diagnosis for ATS can be achieved. Embryo selection should be possible if the gene is known.
Is there any evidence as to which drug is more effective for Andersons
Right now, I don’t believe there is good evidence for one over another. It would require trial and error by an individual to see which is better.
What are the most important side effects of long-term Diamox treatment? My son has taken it since age 3?
Long-term side effects of Diamox are mainly kidney stones. There is some question as to whether or not it also affects calcium metabolism, but my understanding is that this concern is largely theoretical.
Is there a way to get an ATS patient out of a full body attack quicker than 4-5 days?
This is a patient-dependent situation. It depends on the nature of the attack.
Without a cardi-meter can you tell a difference between Hypo and Hyper attack in ATS patient?
Doing a blood draw during an attack should clarify the situation in most cases.
Can a channelopathy give you brisk reflexes and/or upper motor neuron signs? Why?
Conventional dogma would say that we shouldn’t see these things in periodic paralysis. I would not be able to explain the exceptions to this rule readily.
Are kidney stones a risk of PP?
Kidney stones are a risk only if one takes carbonic anhydrase inhibitors for the PP.
What risk does PP have on shingles?
There is no increased risk for shingles with periodic paralysis.
Can a channelopathy affect your antibodies? Example: Low IgA High IgG. Why?
I would not expect an ion channelopathy to affect levels of immunoglobulins.
My family shows signs of PP. Can they get blood test done without a clinical diagnosis?
How will PP affect my long-term muscle control?
Insofar as muscle weakness occurs (either transiently or permanently), muscle control can be adversely affected.
I am moving to Romania to live. Can my Dr. there get information to help me?
Yes. We would be happy to provide your doctor with what information we have. If translation is an issue, consider contacting the U.S. Embassy for translation services.
What are other tests that doctors can perform for diagnosis while waiting for gene testing? What treatments can they give?
If I need to have gall bladder surgery what are my options with anesthesia? Is it safe?
This is a very involved question. Firstly, for which disease? For periodic paralysis, a number of tests can be done ” some recommended, some not:
a) Genetic testing
b) Muscle biopsy
c) Nerve conduction study ” McMannis protocol
d) Blood levels of potassium during and between attacks
e) Reflex testing and strength testing during and between attacks
f) Provocative testing ” either with potassium, carbohydrates, exercise, and/or insulin ” often in a monitored setting
g) Hormone work-up for thyroid and adrenal gland disorders
h) Renal work up for potassium-wasting disorders
i) MRI of muscle to see fat and water content
Therapies depend on the situation. As it stands, that part of the question is too broad to address here.
This discussion would best be had with an expert in periodic paralysis and your anesthesiologist and surgeon. It will depend on what type of periodic paralysis you have. Where possible, depolarizing muscle relaxants should be avoided as well as inhaled anesthetics. Depolarizing muscle relaxants such as succinylcholine are myotoxic. In addition, the membrane might not recover from depolarization and cause or a long-lasting weakness. It is unclear whether or not inhaled anesthetics have to be avoided. As a malignant hyperthermia (MH) crisis has been reported in the literature for a single HypoPP patient (diagnosis genetically never confirmed), we recommend avoidance just to be on the safe side. In a 1990 paper, we have reported equivocal in-vitro contracture test (IVCT) results for HypoPP patients (the IVCT is the gold standard for MH diagnosis); the halothane response was pathologic, the caffeine response normal.
We sent blood to Ulm about 9 years ago and never heard anything. We need SCN4A gene sequencing 1 year ago with our doctor and it was negative. Is there another test we can do to get a more definitive diagnosis?
The specifics of your genetic testing is best addressed directly with Dr. Lehmann-Horn and his associates privately.
Is Daranide something that will be available to try with young children again? I believe it is only used for over 18 now.
Currently, use in children is experimental.
I have 2 boys with possible PP age 7 and11. Both need to have surgery soon for eyes and teeth extractions. What are the risks?
The risks depend on the type of periodic paralysis the boys have.
My Hypo PP started in my late 40's as exercise intolerance. Please explain how this is different that early onset. My docs first thought I had Myasthenia Gravis but then I started with regular episodes of paralysis.
We cannot explain why some people show symptoms later in life and others early in life. If the mutation is known (and by definition has been present since birth), I don’t expect “late-onset” disease to be different from “early-onset”.
A few years ago my doctor told me that during Pp episodes I do not produce a special enzyme in my blood and that this would lead to permanent muscle weakness. Is there such an enzyme? Can he make this abatement?
I am unaware of such an enzyme. He should clarify with specifics. I would be happy to discuss this theory with him.
Is a GI-diet good for people with PP?
Unfortunately, I am unfamiliar with this diet. A diet low in carbohydrates and low in sodium is typically best for hypokalemic periodic paralysis. A diet that avoids high potassium foods is typically best for hyperkalemic periodic paralysis.
What is the difference between stiffness and myotonia?
Stiffness is a sensation of inability to relax muscles, or of muscle tension. Myotonia is a specific type of stiffness defined by a characteristic reading on an electromyogram (EMG).
I have twitching during my attacks why?
We cannot explain twitching and jerks during attacks of periodic paralysis.
If you have 528H genetic defect and no attacks and no weakness How do you titrate medications?
This is an excellent question. This would depend on the individual case and the person’s response to medications. Monitoring of muscle strength over time (say, each 6 months to one year) would be one way to gauge whether strength is deteriorating and if medication needs to be adjusted.
If a woman with AS28H never had attacks but a history in family of muscle weakness is there anything we should be doing to prevent the muscle weakness? Also, same for a man who had one bad attack and now attacks prevented with Diamox
While there is little evidence to support preventing permanent weakness by treating attacks, the current thinking is that people with the gene defect should be on some prophylactic medication and that this medication has a better chance at preventing permanent muscle weakness. Avoiding dietary triggers is also helpful ” that is, avoid high quantities of carbohydrates and salt even if they don’t appear to be causing attacks of weakness.
Is non-specific elevated sed rate to be expected in this disease?
Are there other connective tissue diseases that are commonly associated with Hypo PP or that are confused with Hypo PP?
Hormones and PP Progesterone or other hormone to keep me from getting so sick during my periods? Is there a way to measure these hormones during the month?
I don’t understand this question. If you feel hormonal fluctuations are causing attacks, it would be possible to work with your endocrinologist to measure levels of hormones at different times during the month and during and between attacks. Perhaps you will find a trend.
Diet Coke does it work for everyone with Hypo PP?
Diet Coke is merely one alternative to a low-sugar drink. It is not meant as a therapy for hypokalemic periodic paralysis. Whether or not it causes attacks in an individual is dependent on the individual. Trial and error is worthwhile if Diet Coke is your fancy.
Doctor found soft, squishy muscle tendon during a knee surgery. Doctor is not sure what/why could this be part of damage from HYPO?
It is possible that the muscle was paralyzed during surgery or that it has permanent muscle weakness. Muscle biopsy would be one way to determine this, or possibly MRI. Neither may be necessary.
If someone is taking Spironolactone and potassium 3-6 times a day as 25 mEq, where does potassium go?
Nephrologist claims test did not show excretion in the kidneys.
Potassium can be stored in muscle, and it does not necessarily have to be absorbed. It depends on a person’s total body potassium stores. If the muscles are relatively potassium-depleted, then they can absorb large quantities of potassium.
Questions at the 2020 Webinar for Dr Cannon
Housekeeping genes and PP? How G6PD with absent enzyme activity could impact CACNA1S? sulfa drugs are on avoid list with G6PD. How to treat PP in situation like this?
G6PD deficiency is most commonly associated with blood disorders (anemia, jaundice). Very rarely, it has been associated with muscle breakdown (rhabdomyolysis). There is no known impact of G6PD deficiency on periodic paralysis. Carbonic anhydrase inhibitors are derivatives of sulfonamides and therefore you should check with your primary care physician before going on CAIs. To my knowledge, there is no absolute contra-indication, but it would be prudent to follow the hematologic profile.
For us lay people are Episodic Ataxia and Periodic Paralysis two distinct diagnoses? does the differencial lay in EA: calcium channelopathy & PP is an Potassium channelopathy?
Have other ion channels genes been researched and linked to PP, like IP3 receptors (specifically IP3R3/ITPR3)?
One form of EA is caused by Ca channel mutations (the other by a K channel gene), but it is a completely different Ca channel than the one affected in HypoPP. There is no genetic overlap between HypoPP and EA.
More of a commentary... our family - myself included- have paralysis even with a normal potassium. In fact- my potassium level aim is 4,6 to 5,2. I paralyse under 4,3. We are a large family, not yet having found our defect. But the few that are getting help for PP besides me, need to keep their potassium very high. So high the doctors do not believe it.
Research studies in periodic paralysis has used unbiased gene linkage and whole exome sequencing. These approaches have not identified a defect of IP3 receptors in periodic paralysis. Some early studies also focus on ion channel genes, in general, to search for novel causes of PP. I am not aware of any studies specifically targeted on screening IP3 receptors.
Dr. Jerath - Is the alternating myotonia and paralysis that you are talking about the same as mcyclonic jerking? This happens to me and I've learned in the ER that the treatment for it is to be wrapped in heated blankets.
Changes in serum potassium levels are clearly associated with triggering an episode of PP, but individuals may have their own threshold, and that threshold may vary with time. In practical terms, it’s important to keep a diary to log the events and identify trigger factors. A “normal” potassium level does not exclude a diagnosis of PP.
Can Normokalemic include muscle stiffness up to entire body for the duration of the attack?
Myoclonus is a rapid, brief jerking movement, often of the digits or limbs. The cause is neurological, not a muscle disorder [Steve Cannon].
What is meant by extreme cold....below what sort of temp?...
Yes. Most experts view normokalemic PP as a variant along the paramyotonia congenita <-> hyperkalemic periodic paralysis spectrum. Myotonia is part of the clinical presentation [Steve Cannon].
Can you recommend target values for potassium in hypo patients? In general, can we safely target 5.0 to 6.0
I am not aware of careful studies where skin or muscle temperature was accurately measured. It is clear, however, that immersion of hands in cold water (does not need to be ice cold), drinking a milkshake, or being outside on a winter day can all worsen myotonia.
Can you please explain how you can get hypokpp when there is no one else in the family that has it
The best approach is to keep a record of what levels are needed to optimize your health. Many individuals with HypoPP are asymptomatic when K >= 4.0. Even for a specific individual, there is not a fixed threshold level of K that triggers an attack of weakness. The general trend is usually consistent; namely lower K increases the likelihood of an episode, but it is not like an all or none switch. Another important feature is that the threshold can shift over time (hours to days, not years). With normal kidney function, it will likely be difficult to keep potassium > 5.0
Hello I’m 23 years old from Australia and have been living with Periodic Paralysis since I was 15-16. I still haven’t been properly diagnosed and was wondering if there is any help I can get in Australia or should I organise a video appointment with someone in America?
It has been well documented that new mutations occur spontaneously. Another possibility is the diagnosis might not be recognized for some individuals. Many women with HypoPP do not have episodic attacks of weakness, but still develop fixed weakness later in life.
What about DNA testing for those of us with somewhat unusual symptoms. I have been tested for CACNA1S, RYR1, KCNJ2, SCN4A and 105 other gene defects. No match. I have many common Hypo symptoms but also have high cpk most of the time, muscle swelling especially in my thighs, muscle pain and rarely tea colored urine (Rhabdomyolysis) after bad attacks. Are researchers looking to expand the list of gene defects?
Most academic neuromuscular centers around the world are familiar with periodic paralysis and are equipped to make a diagnosis. Many specialists are also offering telemedicine sessions. I no longer have a clinical practice, perhaps Dr. Jerath can offer some suggestions.
For people with chloride dysregulation, what can be used for anxiety other than a benzodiazepine.
The list of candidate genes you mention includes all of the common genetic causes for PP. The CPK and rhabdomyolysis certainly implicates a muscle problem. Up to 20% of patients with a clinical diagnosis of PP do not have an identified gene defect. Commercial labs typically have a panel of genes to be screen (as you describe). Unbiased screens of the entire genome requires much more effort and is usually performed by a research lab. If there is a large family with affected / unaffected members, or special clinical features; these attributes may encourage a research team to look for new mutations.
Can you explain what's going on in the muscle when exercise is causing fluid retention that leads to weakness?
I’m not sure what you mean by “chloride dysregulation”. Chloride transport problems occur in cystic fibrosis or in a neurological disorder with impaired inhibitory synaptic transmission (stiff-person syndrome). While we strongly believe the chloride distribution across a muscle cell has a strong impact on the risk of PP, periodic paralysis does not have a “chloride dysregulation”, per se.
For example: ironing, making a sauce, ... everything goes well in the beginning. Then a part of my hand starts to swell. This swelling leads to weakness of the hand followed by weakness of the wrist. Furosemide takes away the swelling and brings back the strength.
Same feeling with weakness by waking up; furosemide always helps after some time.
Trying to convince doctors this is not 'functional'.
While studies of Drs. Weber and Lehmann-Horn have shown swelling (edema) of muscle by MRI scan that is worsening during an attack of PP, I am not familiar with visibly apparent muscle swelling during an episode of PP. Interestingly, furosemide is effective at preventing weakness in our HypoPP mouse (for the same reasons I discussed in regard to bumetanide), but in our mouse model it does not help for HyperPP.
What does a muscle biopsy look like for someone with PMW
There are several ways to show “objective” evidence of periodic paralysis. (1) genetic screen, (2) CMAP exercise test (false positive results are extremely rare, so an abnormal response is very meaningful). (3) Needle EMG if you also have myotonia.
If no Myotonia is seen on an EMG, but a person has all the symptoms of Myotonia and HypoKPP (RYR1) should they even mention their Myotonia symptoms?
Muscle fibers are often replaced by fat or fibrous connective tissue, individual muscle fibers have large clear “holes” or vacuoles, ultrastructural studies (electron microscope) may show dilation or redundancy of the transverse tubules and sarcoplasmic reticulum.
I've taken Adderrall for three days and have not had any weakness and triggers are no longer effecting me. I was weak from Dec 2019 until this past Thursday. I stopped Adderall two weeks before a five hour paralysis episode, I did not fully recover from. What effects can a stimulant such as Adderall have on this issue? I have taken the medication for 4 years for ADHD before I gradually weaned off.
When discussing your symptoms with healthcare members, it’s always best to use familiar words that describe what you experience, rather than medical terms. There are other conditions that cause inappropriate muscle contraction in the absence of electrical activity, and therefore is not myotonia (for example Brody disease, which is caused by mutations in a calcium pump). It’s conceivable that a RYR1 defect is causing inappropriate Ca release (and therefore producing contraction) without electrical activity of the muscle fiber.
Do people who have acquired toxicity pass these mutations to their children?
To my knowledge there is no established connection between Adderall usage and periodic paralysis. That said, I would never argue with personal experience.
Since these mutant ion channels involve amino acids, is that why my serine levels are gradually pooling?
Some “acquired” conditions have a component that is heritable. For example red hair and fair skin are heritable and increase the risk of an “acquired” condition, namely sunburn. So, without more specifics it is difficult to answer your question. The only known “acquired” form of periodic paralysis is from thyrotoxicosis.
This as after having the Strongbridge / Invitae testing done to rule out the 4 known variants.
There is no connection between the ion channel mutations in periodic paralysis and amino acid metabolism.
So when will there be anyone who has any more than a passing reference to ATS? The first speaker couldnt even spell it, this speaker (Dr Cannon) has dismissed it & chosen to concentrate on other things... I understand its the rarest thing, but if it doesnt get discussed here (other than to say this is the definition of ATS, and thats great, but we know that info) where will it ever get discussed?.... the answer is... no where. Bit disappointed.
The definition of “variant of unknown significance” evolves are we learn more about specific variations in DNA. At present, there is no available commercial service to perform functional testing of a genetic variant.
In the lodocane study with repeated electrocution which lowered seizure threshold, would that create the sodium mutation.
I discussed new findings in our mouse model of ATS at the 2019 PPA Conference. The talk is available on-line at the PPA site.
As you mentioned, the channels SCN4A and CACNA1S have no appearance in the heart muscle. Is there an explanation for tachycardia and cumulative ventriclar extrasysoles in hypokalemic PP-patients with mutations in these two channels?
No, electric shock is not associated with causing ion channel mutations.
Furthermore I have some specific questions about the replacement of Arginin in CACNA1S but it’s hard to write them just in time here as we’re from Germany. Is it possible to write a mail to you afterwards.
I remember that in the past, insulin was used as a test for PP. Many of my episodes seem to be triggered by a low blood sugar trigger, especially when I am in a hospital situation where I cannot control my diet. Will you explain chemically how this becomes a trigger?
The PPA has an “ask the experts” forum on the web site. This is the best way to submit a question (so that others can also benefit from the answer). I frequently answer questions on this forum.
With regard to the heart issues, there are two thoughts on this. First, SCN4A is expressed at low levels in the heart. Second, skeletal muscle is a huge reservoir for ions in the body (especially potassium). During episodes of PP, ions redistribute into the skeletal muscle and this can have secondary changes on heart electrical properties.
I believe I am more confused now than before tuning in to hear David Griffin. I’ve been told I do have hypokalemic periodic paralysis and I was diagnosed at Henry Ford Hospital in Detroit. The endocrinologist at Henry Ford referred me to The children’s hospital in Detroit and the specialist there did confirm I have hypokalemic periodic paralysis. Will you please confirm with me that there is such a thing as secondary hypokalemic periodic paralysis which is caused by something else causing the symptoms of hypokalemic periodic paralysis? Is this even possible.
Carbohydrate ingestion (sugar or starch), causes insulin release. Insulin binds to receptors on many tissues, but especially muscle and liver, which causes glucose (sugar) uptake in these tissues. This movement of sugar is couple to movement of potassium and so blood potassium levels can decrease substantially.cc
Do you know of a lecture similar to yours (that describes for example how acidity affects muscle function) but for myotonia congenita? Perhaps presented in one of those vimeo presentations.
Primary periodic paralysis occurs when there is an inherited defect in the muscle (ion channel dysfunction). Secondary periodic paralysis is weakness that will occur in normal muscle when there is “external” cause, for example an extreme change of ions in the blood. These severe changes tend to occur in certain forms of kidney disease or if there is an unusual fluid loss (eg very severe diarrhea)
Can I ask the panel: Is there anything to report in ATS research over the last year or two
Acidosis may aggravate myotonia. It is well known that acidosis causes reduced function of chloride channels in muscle (the same ones that are defective in myotonia congenita). In our HyperPP mouse model (SCN4A M1592V), acidosis clearly worsens myotonia. Sorry, I’m not aware of a video presentation on this topic
Bumetanide seems to be as effective as warm down.... but he didnt show them against eachother.. obviously its better not to take medication.. is that correct?
See the PPA Conference from 2019
You mentioned this year and last how valuable input from patience has been directing his research. Has though been given to leveraging the PPA's network to survey patients in mass on symptoms, triggers, and/or treatment/management?
We have found synergistic benefits from using simultaneous approaches to reduce the risk of HypoPP. For example, being both well hydrated and keeping K higher is better than either alone for protection against post-acidosis loss of force. Bumetanide is not yet approved for symptomatic treatment in HypoPP (or ATS). As you say, lifestyle changes are preferred over medication if the result is effective.
I'm in the UK but I'm happy to help with research in any way at all. How can I help you help me?
Thanks for suggesting surveys to assist research efforts. This topic has come up at many prior PPA meetings, and some informal surveys were done. Jake Levitt wrote up the results and published it. I always welcome information on personal experience with PP.
How can I help a patient who is recently diagnosed with PPP?
Dr. Michael Hanna’s group at Univ College London / Queen’s Square Neurological Institute is very active in muscle channelopathy research in the UK. They intermittently have clinical trials and natural history studies. I’m sure they would welcome your participation. I believe the NHS is a good clearinghouse for the announcements.
Education and community engagement are two effective approaches. The PPA is a great place to start!